Obesity and Airway Dysanapsis in Children with and without Asthma

Abstract

Rationale: For unclear reasons, obese children with asthma have higher morbidity and reduced response to inhaled corticosteroids.

Objectives: To assess whether childhood obesity is associated with airway dysanapsis (an incongruence between the growth of the lungs and the airways) and whether dysanapsis is associated with asthma morbidity.

Methods: We examined the relationship between obesity and dysanapsis in six cohorts of children with and without asthma, as well as the relationship between dysanapsis and clinical outcomes in children with asthma. Adjusted odds ratios (ORs) were calculated for each cohort and in a combined analysis of all cohorts; longitudinal analyses were also performed for cohorts with available data. Hazard ratios (HRs) for clinical outcomes were calculated for children with asthma in the Childhood Asthma Management Program.

Measurements and main results: Being overweight or obese was associated with dysanapsis in both the cross-sectional (OR, 1.95; 95% confidence interval [CI], 1.62-2.35 [for overweight/obese compared with normal weight children]) and the longitudinal (OR, 4.31; 95% CI, 2.99-6.22 [for children who were overweight/obese at all visits compared with normal weight children]) analyses. Dysanapsis was associated with greater lung volumes (FVC, vital capacity, and total lung capacity) and lesser flows (FEV₁ and forced expiratory flow, midexpiratory phase), and with indicators of ventilation inhomogeneity and anisotropic lung and airway growth. Among overweight/obese children with asthma, dysanapsis was associated with severe disease exacerbations (HR, 1.95; 95% CI, 1.38-2.75) and use of systemic steroids (HR, 3.22; 95% CI, 2.02-5.14).

Conclusions: Obesity is associated with airway dysanapsis in children. Dysanapsis is associated with increased morbidity among obese children with asthma and may partly explain their reduced response to inhaled corticosteroids.

Keywords: airway dysanapsis; childhood asthma; childhood obesity; pulmonary function.

Figure 1.

Body mass index (BMI) z-score, airway dysanapsis, and lung function. The top six panels show predicted lung function (FEV₁; FVC; forced expiratory flow, midexpiratory phase [FEF_25-75%]; expiratory rate at 50% of FVC [FEF₅₀]; total lung capacity [TLC]; and residual volume [RV]/TLC) and 95% confidence intervals, by BMI z-score and airway dysanapsis status (with dysanapsis in red; no dysanapsis in blue). Children with dysanapsis had lower FEV₁, FEF_25-75%, and FEF₅₀ but higher FVC and TLC. Bottom left panel shows values for k₅₀ and k₇₅. Bottom right panel shows the percentage of children with k₅₀ or k₇₅ values consistent with anisotropic (asymmetric) growth of the lungs and airways. Children with dysanapsis had lower k₅₀ and k₇₅ values, which was more consistent with anisotropic lung and/or airway growth.

Figure 2.

Dysanapsis (dys) and clinical outcomes in children with asthma in CAMP (Childhood Asthma Management Program). Top left panel shows the probability of dysanapsis during 48 months in CAMP by treatment arm in children with dysanapsis at randomization. There were no significant differences between the budesonide or nedocromil and/or placebo arms. Error bars represent 95% confidence intervals. The other three panels show cumulative hazard function of dysanapsis for mild exacerbations (top right), severe exacerbations (bottom left), and requiring more than two prednisone bursts between study visits (bottom right). Children with dysanapsis had a higher risk of exacerbations and prednisone courses during the trial.